|Year : 2021 | Volume
| Issue : 1 | Page : 57-62
Magnitude of subclinical hypothyroidism in type 2 diabetes mellitus – A hospital-based cross-sectional study
Kumari Monika1, Banait Shashank2, Salunkhe Preetam3, Jain Jyoti3
1 Department of Medicine, Shriram Murti Smarak Institute of Medical Sciences, Bareli, Uttarpradesh, India
2 Department of Ophthalmology, Jawaharlal Nehru Medical College, Datta Meghe Institute of Medical Sciences (Deemed to be University), Wardha, Maharashtra, India
3 Department of Medicine, Mahatma Gandhi Institute of Medical Sciences, Wardha, Maharashtra, India
|Date of Submission||10-Jul-2020|
|Date of Decision||03-Nov-2020|
|Date of Acceptance||31-Dec-2020|
|Date of Web Publication||29-Jul-2021|
Dr. Jain Jyoti
Department of Medicine, Mahatma Gandhi Institute of Medical Sciences, Sewagram, Wardha, Maharashtra
Source of Support: None, Conflict of Interest: None
Aim: The aim of the present study was to determine the magnitude of subclinical hypothyroidism (SCH) in patients of >35 years of age presenting with type 2 diabetes mellitus (T2DM) to the tertiary care hospital in rural Central India. Settings and Design: This was a cross-sectional study done in a rural tertiary care hospital conducted for a period of 2 years from October 2016 to September 2018. Materials and Methods: We prospectively enrolled all consecutive T2DM in patients aged ≥35 years in this cross-sectional study in rural hospital in central India. Free T4 and thyrotropin estimation have been done by chemiluminescence and the normal range considered was 0.7–1.8 ng/ml and 0.30–5.5 micron IU/ml respectively. Statistical Analysis: Statistical analysis was done using descriptive and inferential statistics using Student's t-test, Chi-square test, and Mann–Whitney test to compare means, proportions, and medians, respectively P < 0.05 will be considered significant. We analyzed the data by STATA software (Version 16, Stata Corporation, Texas, USA). Results: The mean age of the study population (n = 174) was 57.7 ± 10.4 years and 61.5% were male and 51.7% had high body mass index. The magnitude of SCH was 7.5% among study participants with T2DM (9.3% in male and 4.5% in female). The magnitude of SCH was higher in the elderly age group, 9.2% in 61–80 years age group compared to 6.4% in 35–60 years age group. Conclusion: We concluded from this study that SCH is common in T2DM in our study setting. The prevalence of SCH increases with age, especially elderly female.
Keywords: Serum-free thyroxin, subclinical hypothyroidism, thyroid-stimulating hormone, type 2 diabetes mellitus
|How to cite this article:|
Monika K, Shashank B, Preetam S, Jyoti J. Magnitude of subclinical hypothyroidism in type 2 diabetes mellitus – A hospital-based cross-sectional study. J Datta Meghe Inst Med Sci Univ 2021;16:57-62
|How to cite this URL:|
Monika K, Shashank B, Preetam S, Jyoti J. Magnitude of subclinical hypothyroidism in type 2 diabetes mellitus – A hospital-based cross-sectional study. J Datta Meghe Inst Med Sci Univ [serial online] 2021 [cited 2021 Sep 16];16:57-62. Available from: http://www.journaldmims.com/text.asp?2021/16/1/57/322621
| Introduction|| |
Type 2 diabetes mellitus (T2DM) and thyroid disorders are the two most common endocrine disorders encountered in clinical practice and are a major growing cause of morbidity and premature mortality. The Indian Council for Medical Research-India Diabetes national study, conducted in three states Maharashtra, Tamil Nadu, and Jharkhand reported that there are 62.4 million people with T2DM and 77 million people with prediabetes belongs to India.
Subclinical hypothyroidism (SCH) is a condition which is defined biochemically as a normal serum free thyroxin (fT4) concentration in the presence of an elevated serum thyrotropin (TSH) concentration. In population-based studies and the Cochrane Database of Systematic Reviews, mentioned the prevalence of SCH ranges from 4% to 15%. The prevalence rises with age, higher in females than males and is lower in blacks than in whites.,,,, SCH is often asymptomatic, however, nearly 30% of patients may have symptoms suggestive of hypothyroidism. Possible consequences of SCH include increased risk of cardiovascular disease,,,, elevation in total and low-density lipoprotein cholesterol, neuropsychiatric symptom, and progression to overt symptomatic hypothyroidism in approximately 2%–5% cases annually.,
The association between T2DM and SCH is well known. Several reports documented a higher than normal prevalence of SCH in the diabetic population. Diabetes mellitus and thyroid disorders have been shown to mutually influence each other. SCH has been reported to be associated with increased risk of endothelial dysfunction, nephropathy, coronary heart disease, and diabetic retinopathy in patients with T2DM.,
It is recommended to do thyroid profile in all patients with T2DM, similar to the recommendation in T1 DM. To our knowledge, no study has been reported from the rural India regarding the magnitude of SCH in this region.
The aim is to evaluate the magnitude and correlates of SCH in patients of more than 18 years of age presenting with T2DM to the tertiary care hospital in rural India.
The main objectives are as follows:
- To determine the magnitude of SCH in patients of T2DM to the tertiary care hospital
- To assess the correlates of SCH in patients of T2 DM.
| Materials and Methods|| |
Study design and setting
This was a cross-sectional study conducted in the Department of Medicine at MGIMS, a 920-bedded, teaching, tertiary care rural hospital for a period of 2 years from October 2016 to September 2018. The study was approved by the Institutional ethics committee (IRB00003623). We obtained written informed consent from all study participants before enrolling them in the study. The sample size was calculated as 174 with the expected prevalence of SCH in T2DM to be 13% (5% to 22%).,
In our study, we enrolled all consecutive patients of ≥35 years of age, admitted with a history of T2DM from October 2016 to September 2018, resident of Wardha district, in this cross-sectional study. Type 2 Diabetes Mellitus was defined as per the American Diabetes Association. Study participants were also included in the study, based on the history of T2DM provided by them or if they were on oral hypoglycemic drugs.
- Diabetic patients known to have thyroid disorder i.e., hypothyroidism, hyperthyroidism or taking any treatment for thyroid
- Patients had any surgery or radiation for thyroid
- Patents taking anticonvulsant drugs (Carbamazepine, Oxcarbazepine, Phenytoin, Phenobarbital, and Primidone) and on Aspirin therapy
- Pregnancy and gestational diabetes mellitus
- Patients not giving consent for the study.
All study participants included in the study underwent a relevant clinical history and examination. Interview of all study subjects was undertaken by the same research associate and was pilot tested. Demographic data including age, sex, and body mass index (BMI). Body mass index was calculated by standard formula and reference values were according to the World Health Organization (WHO). For the analysis study participants were categorized into two groups, having normal BMI <25 Kg/m2 and high BMI ≥25 Kg/m2. We elicited information about the duration of diabetes and study participants were categorized in two categories according to the total duration of diagnosis of T2DM, as <10 years and >10 years.
Assessment of clinical features of subclinical hypothyroidism
Symptoms of SCH, for example, tiredness, intolerance to cold, hair loss from the scalp, difficulty in concentrating and poor memory, constipation, weight gain with poor appetite, hoarse voice, paresthesia, menstrual history in female were obtained during baseline interview. The study participants have been examined clinically for signs of hypothyroidism, i.e., dry coarse skin, cool peripheral extremities; myxedema (puffy face, hands, and feet), diffuse alopecia, bradycardia, and delayed relaxation of ankle reflex were noted.
Blood sugar estimation
Blood samples were obtained in fasting state to measure fasting blood sugar. Blood glucose was measured using the venous sample, in central biochemistry laboratory using auto analyzer (XL-300) by glucose oxidase peroxidase method.
Thyroid function test
Blood samples for TSH and fT4 were collected in plain tubes and serum-free from hemolysis was stored at 2°C–8°C. Free T4 and TSH estimation have been done by chemiluminescence. SCH was defined as TSH value >5.5μ IU/ml and normal fT4 (0.7–1.8 ng/ml). Overt hypothyroidism was defined as TSH value >5.5 μ IU/ml and fT4 value <0.7 ng/ml.
We entered the data electronically by Microsoft Excel and analyzed by STATA software (Version 16, Stata Corporation, Texas, USA). The magnitude of SCH in T2DM study subjects was calculated as percentage. The means was compared with a t-test and proportions with Chi-square test. A level of P < 0.05 was used to indicate statistical significance in all analyses.
The Institutional Ethics Committee of DMIMSDU has approved the Research work proposed to be carried out at Jawaharlal Nehru Medical College, Sawangi(M), Wardha. Date: 8th March 2016 with Reference no DMIMS(DU)/IEC/2016-17/980.
| Results|| |
Study participants baseline characteristics
A total of 368 cases of T2DM were screened during the study period, out of which 194 study met the exclusion criteria and 174 participants were included in the study as shown in [Figure 1].
The baseline characteristics of the study subjects are summarized in [Table 1]. Majority (62.6%) of study participants belonged to 35–60 years of age with a mean age of 57.7 ± 10.4 years. Among study participants, majority (61.5%) were male and 51.7% had high BMI. The duration of diabetes was <10 years in majority (83.9%) of study participants. Symptoms of hypothyroidism were found in 64.4% of study participants and tiredness and generalized weakness were the most common (62.1%) presentation. Other symptoms found were constipation in 34.5%, poor appetite in 33.3%, dyspnea in 26.4%, weight gain in10.9%, dry skin in 8%, and hoarseness of voice in 4%, while signs of hypothyroidism were found in 19% of study participants. The most common sign was dry coarse skin in 11.5% and other signs were peripheral edema in 10.9% and delayed relaxation of ankle reflex in 1.1%. Mean hemoglobin of study participants was 12.6 ± 1.3 g/dl. Fasting blood sugar was found to be abnormal in 76.6% and postprandial blood sugar was abnormal in 62% [Table 1].
Magnitude of subclinical hypothyroidism among type 2 diabetes mellitus study participants
Levels of TSH were found low in 1.7% (male 0.9%, female 3%), normal in 89.1% (male 88.8%, female 89.5%) and high in 9.2% (male 10.3%, female 7.5%). Free T4 was low in 7.5% (males 7.55, females 7.5%), normal in 90.2% (male 91.6%, female 88%), and high in 2.3% (male 0.9%, female 4.5%) [Table 2]. The magnitude of SCH was 7.5% among study participants with T2DM (9.3% in male and 4.5% in female). The magnitude of SCH was higher in elderly age group, 9.2% in 61–80 years age group compared to 6.4% in 35–60 years age group.
|Table 2: Thyroid stimulating hormone and free T4 level among study subjects by gender (n=174)|
Click here to view
| Discussion|| |
This cross-sectional study which was carried out among T2DM study subjects, the magnitude of SCH was found to be 7.5%. In previous studies, the reported incidence of SCH in T2DM varies from 4.1%–18.1% [Table 3]. Various studies have reported a similar prevalence of SCH among T2DM patients in their settings.,,,,,,,, However the magnitude of SCH in patients with T2DM in our study was higher as compared to some studies.,, This variation in magnitude is mainly because of the methods used for measurement of TSH and fT4, different cut off for TSH to diagnose SCH, and different study settings as the population in the present study is predominantly rural and hence carries different risk factors. In a study from Jordan, T2DM patients with ketosis were not included and the TSH level to define SCH was lower compared to our reference range (5 μIU/ml vs. 5.5 μIU/ml). Perros et al. included both T1DM and T2DM diabetic patients from the outpatient setting while we included only T2DM patients from the inpatient setting. The magnitude of SCH in our study was lower compared to some studies.,,,,,, The difference in magnitude of SCH could be due to different age group of the study population studied, different reference range of TSH and FT4 taken and difference in the geographical area. Summary of some of the sampled studies whose results have been compared with the present study are shown in [Table 3].
|Table 3: Prevalence/magnitude of subclinical hypothyroidism in various studies|
Click here to view
In our study, elderly study participants had a higher magnitude (9.2%) of SCH, compared to younger study participants (6.4%), which was in accordance with previous studies.,,, The reason for the increased prevalence of SCH with age is explained by the possibility of increased chances of autoimmunity with increasing age. In the present study, we found a higher occurrence of SCH in male study participants as compared to female study participants, however, in elderly females, it was more than elderly males. Many previous studies mentioned the prevalence of SCH to be higher in women than in men in contrast to our findings.,,,,,,,,, Canaris et al. and Tunbridge et al., concluded that prevalence of SCH may increase to 15% to 18% in women who are over 60 years of age.,,, In this study, we did not found any association of SCH with BMI, which was is similar to the study conducted by Al-Geffari et al. In a community-based study among 1944 adults, who were followed for 11 years, no statistically significant association between change in serum TSH concentrations and weight change was found. In contrast to our study results few studies found a significant association of BMI >25 Kg/m2 and increase in serum TSH., We did not found any statistically significant association between the duration of diabetes and SCH. Similar findings were also reported by Ravishankar et al. However, Al-Geffari et al. found positive association between duration of diabetes and SCH.
This observational study for the magnitude of SCH among T2DM is one of the few from rural India. Being a single-center study had some inherent methodology which provides credibility to the study. The sample size of the study population was adequate. Our study has few limitations also. The study samples were derived from patients visiting to a tertiary care hospital, and hence, the results cannot be generalized to a population in the community. The possibility of selection bias cannot be ruled out. The possibility of sick euthyroid syndrome cannot be ruled out, as we have not followed these study subjects. We propose that elderly patients with T2DM should be screened for SCH as early management of SCH in patients with T2DM may prevent associated morbidity and mortality.
This observational study for the magnitude of SCH among T2DM is one of the few from rural India. We used standard definitions for SCH and T2DM and being a single-center study had some inherent methodology which provides credibility to the study. The sample size of the study population was adequate. We propose that elderly patients with T2DM should be screened for SCH as early management of SCH in patients with T2DM may prevent associated morbidity and mortality.
The possibility of selection bias cannot be ruled out. Although the consequent patients of T2DM were screened in the present study, all of them could not be included, as in few study participants thyroid profile results were not available. The possibility of sick euthyroid syndrome cannot be ruled out, as we have not followed these study subjects.
| Conclusion|| |
We concluded from this study that SCH is common in T2DM in our study setting. The prevalence of SCH increases with age, especially elderly female. Although we have not found any significant association of age and sex with SCH, further large community-based screening study needs to be done. [37,,,,
Financial support and sponsorship
This study was financially supported by the Kasturba health society, Mahatma Gandhi Institute Of Medical Sciences, Sevagram, Wardha Maharashtra.
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3]